Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

[1]  Kiseok Jang,et al.  Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial Host Defense via PKCα , 2017, PLoS pathogens.

[2]  Alimuddin Zumla,et al.  Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis , 2016, BMC Medicine.

[3]  S. Kaufmann,et al.  Host-directed therapies for infectious diseases: current status, recent progress, and future prospects , 2016, The Lancet Infectious Diseases.

[4]  Young-Ha Lee,et al.  Toxoplasma gondii GRA7-Induced TRAF6 Activation Contributes to Host Protective Immunity , 2015, Infection and Immunity.

[5]  R. Raqib,et al.  Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial , 2015, PloS one.

[6]  S. Abdulla,et al.  Towards host-directed therapies for tuberculosis , 2015, Nature Reviews Drug Discovery.

[7]  Ho-Yeon Song,et al.  Ursolic Acid Activates Intracellular Killing Effect of Macrophages During Mycobacterium tuberculosis Infection. , 2015, Journal of microbiology and biotechnology.

[8]  A. Spanevello,et al.  New anti-tuberculosis drugs and regimens: 2015 update , 2015, ERJ Open Research.

[9]  Nuno Empadinhas,et al.  Autophagy in the fight against tuberculosis. , 2015, DNA and cell biology.

[10]  Alimuddin Zumla,et al.  Inflammation and tuberculosis: host‐directed therapies , 2015, Journal of internal medicine.

[11]  F. Milián-Suazo,et al.  What Can Proteomics Tell Us about Tuberculosis? , 2015, Journal of microbiology and biotechnology.

[12]  Nalini Singh,et al.  Cellular therapy in tuberculosis. , 2015, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[13]  Myung-Shik Lee,et al.  New mechanisms of metformin action: Focusing on mitochondria and the gut , 2015, Journal of diabetes investigation.

[14]  R. Jain,et al.  Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery , 2015, Proceedings of the National Academy of Sciences.

[15]  J. Wolchok,et al.  Immune Checkpoint Blockade in Cancer Therapy. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Bernard Klein,et al.  Interleukin-6 as a Therapeutic Target , 2015, Clinical Cancer Research.

[17]  G. Kaplan,et al.  Metformin as adjunct antituberculosis therapy , 2014, Science Translational Medicine.

[18]  A. Sher,et al.  Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk , 2014, Nature.

[19]  Marieke J. van der Werf,et al.  Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement , 2014, European Respiratory Journal.

[20]  T. R. Raghunand,et al.  An immunomodulatory role for the Mycobacterium tuberculosis region of difference 1 locus proteins PE35 (Rv3872) and PPE68 (Rv3873) , 2014, The FEBS journal.

[21]  M. Shong,et al.  The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy , 2014, Autophagy.

[22]  T. Hawn,et al.  Host-Directed Therapeutics for Tuberculosis: Can We Harness the Host? , 2013, Microbiology and Molecular Reviews.

[23]  D. Mitra,et al.  Inhibiting the programmed death 1 pathway rescues Mycobacterium tuberculosis-specific interferon γ-producing T cells from apoptosis in patients with pulmonary tuberculosis. , 2013, The Journal of infectious diseases.

[24]  P. Cardona,et al.  Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. , 2013, The Journal of infectious diseases.

[25]  Alimuddin Zumla,et al.  Advances in the development of new tuberculosis drugs and treatment regimens , 2013, Nature Reviews Drug Discovery.

[26]  I. Sanne,et al.  Costs of inpatient treatment for multi‐drug‐resistant tuberculosis in South Africa , 2013, Tropical medicine & international health : TM & IH.

[27]  T. File,et al.  An evidence-based review of linezolid for the treatment of methicillin-resistant Staphylococcus aureus (MRSA): place in therapy , 2012, Core evidence.

[28]  D. Follmann,et al.  Linezolid for treatment of chronic extensively drug-resistant tuberculosis. , 2012, The New England journal of medicine.

[29]  K. Döhner,et al.  Abelson Tyrosine Kinase Controls Phagosomal Acidification Required for Killing of Mycobacterium tuberculosis in Human Macrophages , 2012, The Journal of Immunology.

[30]  E. Westhof,et al.  Structure-Activity Relationships among the Kanamycin Aminoglycosides: Role of Ring I Hydroxyl and Amino Groups , 2012, Antimicrobial Agents and Chemotherapy.

[31]  Alfred J. Zullo,et al.  Old antibiotics target TB with a new trick. , 2012, Cell host & microbe.

[32]  Young Kil Park,et al.  Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. , 2012, Cell host & microbe.

[33]  C. Jagannath,et al.  Immunoregulatory Role of GM-CSF in Pulmonary Tuberculosis , 2012 .

[34]  P. Karakousis,et al.  Old and New TB Drugs: Mechanisms of Action and Resistance , 2012 .

[35]  E. Willery,et al.  Structural activation of the transcriptional repressor EthR from Mycobacterium tuberculosis by single amino acid change mimicking natural and synthetic ligands , 2011, Nucleic acids research.

[36]  D. Kalman,et al.  Imatinib-sensitive tyrosine kinases regulate mycobacterial pathogenesis and represent therapeutic targets against tuberculosis. , 2011, Cell host & microbe.

[37]  Ying Zhang,et al.  Pyrazinamide Inhibits Trans-Translation in Mycobacterium tuberculosis , 2011, Science.

[38]  J. Adams,et al.  Immunomodulation by vitamin D: implications for TB , 2011, Expert review of clinical pharmacology.

[39]  T. Kishimoto,et al.  Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-α Antibody in Mice , 2011, Clinical & developmental immunology.

[40]  Marcos Abdo Arbex,et al.  Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 1: first-line drugs. , 2010, Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia.

[41]  Marcos Abdo Arbex,et al.  Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha , 2010 .

[42]  K. Zaman,et al.  Tuberculosis: A Global Health Problem , 2010, Journal of health, population, and nutrition.

[43]  R. Wallis,et al.  Adalimumab treatment of life-threatening tuberculosis. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[44]  O. Rivero-Lezcano.  Cytokines as immunomodulators in tuberculosis therapy. , 2008, Recent patents on anti-infective drug discovery.

[45]  R. Green,et al.  Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome. , 2007, Journal of molecular biology.

[46]  Vojo Deretic,et al.  Mechanisms of action of isoniazid , 2006, Molecular microbiology.

[47]  F. Baquero,et al.  In vitro activity of linezolid against Mycobacterium tuberculosis complex, including multidrug-resistant Mycobacterium bovis isolates. , 2006, International journal of antimicrobial agents.

[48]  R. Wallis.  Reconsidering adjuvant immunotherapy for tuberculosis. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[49]  B. Nelson.  IL-2, Regulatory T Cells, and Tolerance , 2004, The Journal of Immunology.

[50]  V. Jarlier,et al.  Mycobacterium tuberculosis DNA Gyrase: Interaction with Quinolones and Correlation with Antimycobacterial Drug Activity , 2004, Antimicrobial Agents and Chemotherapy.

[51]  R. Badaró,et al.  Use of Rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial. , 2003, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[52]  C. Locht,et al.  Activation of the pro-drug ethionamide is regulated in mycobacteria. , 2000, The Journal of biological chemistry.

[53]  V. Kapur,et al.  Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis , 1997, Journal of bacteriology.

[54]  B. Johnson,et al.  Clinical and immune responses of tuberculosis patients treated with low-dose IL-2 and multidrug therapy. , 1995, Cytokines and molecular therapy.

[55]  M. Denis,et al.  Granulocyte-macrophage colony-stimulating factor restricts growth of tubercle bacilli in human macrophages. , 1990, Immunology letters.

[56]  J. McManus,et al.  Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. , 1973, The New England journal of medicine.

[57]  THE WORLD HEALTH ORGANIZATION , 1954 .

[58]  D. Mitchison,et al.  Streptomycin Resistance in Pulmonary Tuberculosis , 1948, British medical journal.

[59]  L. Gabbasova,et al.  Global tuberculosis report (2014) , 2014 .

[60]  M. Jure-Kunkel,et al.  CTLA-4 blockade in tumor models: an overview of preclinical and translational research. , 2013, Cancer immunity.

[61]  T. Ottenhoff,et al.  Control of human host immunity to mycobacteria. , 2005, Tuberculosis.

[62]  E. Bouza,et al.  Linezolid: pharmacokinetic characteristics and clinical studies. , 2001, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[63]  A. Rattan,et al.  Multidrug-resistant Mycobacterium tuberculosis: molecular perspectives. , 1998, Emerging infectious diseases.

[64]  G. Kaplan,et al.  rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo. , 1997, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[65]  S. Cole,et al.  Mechanisms of drug resistance in Mycobacterium tuberculosis. , 1994, Immunobiology.